NSAIDs and Osteoarthritis: Pharmacology, Side Effects, and Treatment Strategies

What is the most common joint disorder in the US?

osteoarthritis

preferred first line for osteoarthritis

tylenol

COX-1

present in all cells expressed continuously

COX-2

synthesized in response to pain and inflammation, not always present

3 NSAIDS

aspirin, ibuprofen, meloxicam

NSAIDS provide both:

analgesic and anti-inflammatory actions

What is prescribed with NSAIDs for patients with GI upset

H2 blocker or take with food or milk

What should provider be vigilant about with NSAID Rx?

hypersensitivity reactions like history of asthma, allergies, nasal polyps

NSAIDS and pregnancy

dont use in third trimester to avoid closure of ductus arteriosus

NSAIDs and surgery

stop one week before surgery to avoid prolonged bleeding

NSAIDs patient education

hepatic failure, GI ulcers, avoid alcohol

clinical uses of NSAIDS in osteoarthritis

reduction of fever, pain and inflammation

Celecoxib

COX-2 inhibitor

NSAIDs for osteoarthritis 9

Ibuprofen, naproxen, diclofenac (voltaren gel), indomethacin, sulindac, miloxicam, ketorolac, etodolac, celecoxib

MOA of NSAIDS

inhibit prostaglandin synthesis by inhibiting cyclo-oxygenase (cox)

NSAIDS adrs

edema, GI bleed and ulcers, abdominal pain, prolonged bleeding, increased liver enzymes

COX-2 adrs

less GI side effects

NSAID special side effect at high doses

salicylism (HA, dizziness, hyperventilation, hearing loss, hyperthermia)

salicylism treatment

sodium bicarb alkalanizes urine to increase elimination, increase pH=draw acid into urine, or gastric lavage or emesis within 1-2 hours

NSAIDS other med interactions

increased hypoglycemia and risk of bleeding

who should not take NSAIDs

renal issues, HF, HTN

aspirin

acetylsalicylic acid

aspirin MOA

analgesic, antipyretic, and anti inflammatory at higher doses, antiplatelet, acetylation

aspirin acetylation effect

reduces formation of thromboxane A2 to promote platelet aggregation

inhibitory effect of aspirin

irreversibly inhibits platelets that lasts 8 days

aspirin side note for heart attack use

DO NOT use enteric coated aspirin because they wont work the same

Aspirin pharmacokinetics

at lower doses metabolism is first order at higher doses it becomes zero order so repeated dosing will greatly increase concentration

aspirin secretion

excreted as urine because alkalization increases excretion

Ibuprofen, meloxicam MOA

Reversible inhibition of COX-1 and COX-2

Chewable ibuprofen contains

aspartame

meloxicam special adr

SJS

tylenol

acetaminophen

preferred drug for mil/mod pain w/o inflammation

acetominophen

acetominophen and COX-1 and 2

no anti-inflammatory or GI effects

tylenol adr

hepatotoxicity and increased liver enzymes

acetaminophen toxicity

hepatic necrosis course of 7 days

acetominphen toxicity treatment med

N-acetylcysteine given less than 24 hours post ingestion

Rumack matthew nomogram

determines treatment for tylenol toxicity, time from ingestion and concentration

misoprostol

antiulcer decreases side effects caused by NSAIDs

Misoprostol MOA

PGE1 analog. Increase production and secretion of gastric mucus barrier. Decrease acid production.

misoprostol adr

miscarriage, avoid in pregnancy, increased K levels with K sparing diuretics

celecoxib unique lack of activity

no antiplatelet activity

Celecoxib ADRs

leg edema, HTN, stroke, MI, rash, RENAL TOXICITY

celecoxib risks

worse for renal toxicity, black box warning for CV thrombotic events, CABG surgery

Rheumatoid Arthritis (RA)

increased interleukin 1 and TNF, synovial proliferation and erosion of cartilage and bone

RA treatment general

DMARDs slow progression

mild RA treatment

glucocorticoid joint injections, prednisone

pts start DMART tx with what med

methotrexate

traditional DMARTs

methotrexate, leflunomide, hydroxychloroquine

biologic DMARDs

TNFIs, ILIs and JAKis